2026-08-29T22:06:57Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/88762024-11-30T01:12:33Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Lopez, Sophie author Voisset, Edwige author Tisserand, Julie C author Mosca, Cyndie author Prebet, Thomas author Santamaria, David author Dubreuil, Patrice author De Sepulveda, Paulo author 2016-08-09 CDK4/CDK6 and RB proteins drive the progression through the G1 phase of the cell cycle. In acute myeloid leukemia (AML), the activity of the CDK/Cyclin D complex is increased. The mechanism involved is unknown, as are the respective roles played by CDK4 or CDK6 in this process. Here, we report that AML cells carrying FLT3-ITD mutations are dependent on CDK6 for cell proliferation while CDK4 is not essential. We showed that FLT3-ITD signaling is responsible for CDK6 overexpression, through a pathway involving the SRC-family kinase HCK. Accordingly, FLT3-ITD failed to transform primary hematopoietic progenitor cells from Cdk6-/- mice. Our results demonstrate that CDK6 is the primary target of CDK4/CDK6 inhibitors in FLT3-ITD positive AML. Furthermore, we delineate an essential protein kinase pathway -FLT3/HCK/CDK6- in the context of AML with FLT3-ITD mutations. Oncotarget. 2016;7 (32):51163-51173. 10.18632/oncotarget.9965 1949-2553 1949-2553 Oncotarget 27323399 http://hdl.handle.net/20.500.12105/8876 AML SRC Oncogene Palbociclib Protein kinase Signaling An essential pathway links FLT3-ITD, HCK and CDK6 in acute myeloid leukemia